Ashokrao

           

NOVA
Business
Challenge
 Biotechnical
Business
 Ashok
Rao
        

2009

    Rao,  2  The Social Impact of Neurological Diseases  Unless we do something to prevent it, in the next forty years we are facing an Figure 1

epidemic of neurologic diseases on a global scale. Today, few countries (nestled within prosperous

% of population (in blue) over age sixty-five today.

Europe) have over twenty percent of the population above the age of sixty-five. In fifty years, all countries (with the exception of those on the African continent) will have more than twenty percent of the population above the age of sixty-five. Figure 1 and 2 illustrate this change. For twelve thousand years the age distribution has resembled a pyramid, with the oldest on the top; by

Figure  2  % of population (in blude)  over age sixty  ‐ five in  2050.

2050 it will become a column and slowly start to invert (figure 3), as our average life expectancy increases at an average of five hours per day. For

 

those above the age of sixty-five the chances of contracting Alzheimer’s or Parkinson’s

Figure 3  Inversion of age distribution  from 10,000 B.C. through 

    Rao,  3  increases exponentially. By 2050 over thirty-two million Americans (ten percent of our current population) will be above the age of eighty and half of

Figure  4   Depicts increase in Alzheimer’s and Parkinson’s 

them will have Alzheimer’s while another three million will have Parkinson’s. Currently Alzheimer’s, Parkinson’s, and various other neurological diseases that we have no cure for cost us a third of a trillion dollars per year, and we will be well   over the twelve zero benchmark by

Condition 

Total Cases  (U.S) 

Cost Per Year  in USD 

All Depressive  Disorders 

20.5 million 

44 billion 

Alzheimer’s  Disease 

4.5 million 

100 billion 

Huntington’s  Disease 

30,00 

2 billion 

diseases, says his team is working on a

Parkinson’s  Disease 

1 million 

5.6 billion 

drug that acts as a “molecular scotch

ALS 

35,000 

3 billion 

tape.” Such a medicine would prevent

MSA 

250,000 

10 billion 

the protein from tangling up, and hence

Traumatic Head  Injury 

5 million 

56.3 billion 

Multiple  Sclerosis 

2.5 million 

9.5 billion 

diseases, which affect completely

Spinal Cord  Injury 

250,000 

10 billion 

different areas within the brain, are also

Stroke 

4.7 million 

1 billion 

Schizophrenia 

2 million 

32.5 billion 

Total Cost 

 

334.9 billion 

U.S. GDP 

 

~12.7 trillion 

2050. Alzheimer’s Disease is the result of a protein that folds itself in the wrong way, like demented origami. Greg Petsko, a neurologist working with such

preventing the death of so many brain cells. Interestingly, other neurological

    Rao,  4  subject to these “tangles.” Petsko believes that all of the diseases that fall under this category are different manifestations of the same, underlying disease. Another connection that few people pursue is the connection with Alzheimer’s and cancer. While scientists are not sure why, there is an amazingly low incidence of cancer within Alzheimer’s patients. The effects of a drug for Alzheimer’s may have miraculous other effects. As today’s healthcare system crashes while drug development prices skyrocket it is safe to say our current modus operandi is unsustainable at best. A conservative estimate of the cost of treating an elder person with Alzheimer’s exceeds twenty-two thousand dollars. As the age pyramid inverts we must find a more efficient manner to deal with such disease. As stated above, when the treatment of those above sixty-five (a group which, naturally, cannot put anything back into our system) is moving towards ten percent of our GDP the impact it will have on our next working generation is tremendous. With our current system in ashes healthcare has become a political issue, and one that must be mended. The following graph depicts our current healthcare to GDP ratio.

Figure 5 

 

    Rao,  5  Almost fourteen percent of our GDP is based on our healthcare system. By 2050 the money spent for just the treatment of neurological treatment of elders will be approaching ten percent of our current GDP (figure 5). According to Petsko the future for this will lie not in the government but in privatized philanthropy and private institutions. The question is not only one of scientific proportions, but also of financial, economical, and global proportions. Nestled within the question is how we as a world will deal with this. Elder America receives much medical attention, but the next generation of old must begin today. Petsko believes there are a few important (and easy) steps one can take. Don’t want Parkinson’s? o Have another Latte. 

Caffeine’s potential beneficial effects may help

o Try to avoid head injuries o Try to avoid the avian flu Don’t want Alzheimer’s? o Eat more fish (or at least ingest Omega Three). o Keep your blood pressure low, as chronic high blood pressure is the single largest risk factor for Alzheimer’s. o Stay cognitively stimulated; this is a pivotal aspect of staying mentally healthy. o Exercise

    Rao,  6  Taking such precautions will greatly lessen the risk of contracting neurological diseases. For today’s victims such precautions have little effect (as they are precautions) but the risk of a high incidence in tomorrow’s old will lessen significantly if we instill these measures in today’s young. Unfortunately, most people need an extrinsic motivation to maintain a routine method in which they follow such precautions. Many insurance companies already provide a benefit (however insignificant) for those who frequently workout. Luckily, increasing the stakes does not make it a zero-sum game. Health insurance firms must do this to prevent its overall expenditure on major healthcare operations. It will benefit the consumer in two different ways: a) lower premiums and b) healthier people. The former will translate to a greater spending budget for the people that results in a stronger economy. The latter will result in a happier society (a gift in and of itself), and happy societies tend to spend more. The burden does not have to be carried solely by United Healthcare and its peers, but also by any form of corporate bodies. Foods that are cholesterol rich should be limited while foods that help balance the cholesterol in my arteries should be promoted. Hy-Vee (the local grocery chain) should give all members a “fitness card” that allows those who workout over five hours perweek get a ten percent discount while those who workout over ten hours per week get a fifteen percent discount. Another interesting strategy would be to reduce the price of a steak for every box of Cheerios one buys. Physical Education reform is another major issue. While many other “reforms” penetrate our minds, this is more important than it may seem. Studies show that people are far more likely to be physically active as they age if they a) learn the importance of it when they are young and b) if they were active when they were young. I cannot attest to

    Rao,  7  any other countries, but in America we are required to do “gym” at varying intervals. Pre high school “gym” includes the morphing into a “gym uniform” and playing ball. While such activity has its purpose it does not provide the physical exercise that one needs. Gym class needs to engage daily and consist of sustained aerobic activities. Running is a great start. High school students are motivated in different ways than are working parents, and we must recognize this as a society. While it is questionable for the school to provide an overall increase in the cumulative GPA for those students who participate in sports, the societal benefits would far outweigh the questionable morals. Colleges partake in an extreme version of my proposed plan; never fail the quarterback (or the basketball captain at Duke). My idea is not limited to those good at such sports, but to those who work hard and sweat harder. In Alzheimer’s, neurons in the brain die by apoptosis; apoptosis is primarily induced by a beta-amyloid that is a toxic protein that perpetuates the apoptosis. Purinederivatives have been proven to have protective effects on various cell types. Eva Vertes hypothesized that a purine-derivative known as RPI-069 would protect neurons against pathogenic stimuli, a beta-amyloid involved in Alzheimer's development. Vertes investigated this hypothesis in a series of experiments. According to her research, the proportion of apoptosis decreased by sixty percent. These results suggest that RPI-069 is effective in protecting neurons against beta-amyloid. Research in this field may provide one of the greatest leaps in Alzheimer’s history. Alzheimer’s is now being increasing recognized as type three diabetes, and the research behind this claim is another key to unlocking the secrets of this disease. As mentioned earlier, the toxic protein beta-amyloid ruins the neurons and synapses that

    Rao,  8  maintain a strong memory. A research team from Northwestern University found a relation between insulin and such synapses. The scientists retrieved cells from the hippocampus of the brain and treated it with insulin and Avandia, an insulin-sensitizing drug. Subsequent to binding amyloid-beta, synapses lose their capability to respond to incoming information, resulting in memory loss. Scientists found that the insulin blocked the amyloid-beta protein from binding with the synapses by blocking the protein’s receptors. Avandia catalyzed the effect of the insulin. Scientists at the University of Southern California concluded that those who developed diabetes prior to age of sixtyfive had one hundred twenty-five percent greater chance of contracting Alzheimer’s. Another step in understanding and maybe identifying Alzheimer’s is to understand Biomarkers. A study from Washington University in St. Louis shows that studying biomarkers with patients who have at least one parent who has Alzheimer’s while using patients who have no parents who have Alzheimer’s is crucial to developing vaccination or prevention. Scientists at Washington University have found a compound that allows imaging devices to locate beta-amyloid. With this new generation of imaging devices scientists are hopeful to find biomarkers. While it is for the private sector to carry out such operations, our government must urge such actions As the clock ticks the closer our society becomes towards such a large elder population. It is my belief that the government must act now. Economically, we are in an unprecedented slump and healthcare is a major part of this recession. As the main body of a country, it is for the government to push effective strategies, which are then carried out by private sectors. Economic stimulus is largely ineffective if we throw away money. Corporate stimulus with specified conditions, however, will be

    Rao,  9  exponentially more effective. Giving United Healthcare (or any other company which recognizes the same goals) the money to provide the consumers a lower premium if they follow certain guidelines (until the benefits for the company itself settle in) will motivate such institutions to promote such precautions. The government must also promote a prioritized healthcare system. While I do not know enough to comment on how each category is prioritized, we need to instill a lower limit on today’s elder healthcare while giving the forty percent of uninsured American’s a better plan. Not giving a man the treatment he needs may be considered unethical, but it is something that will increase the integrity of our society as a whole. I came to this realization after recent events; and watching my grandfather’s treatment after a hemorrhagic stroke. Minutes after “feeling sleepy” he was in the intensive care unit which cost about two thousand dollars per night. After that he spent a week in the hospital rehab center that cost around eight hundred per night. For nearly a month after that he lived in a nursing home that helped him “transition” which cost five thousand for the month. The treatment cost more than sixteen thousand dollars. I am not an ethicist and such a thought is troubling, but one would have been able to save hundreds of children from dying with the same money. After digesting this hard and rocky thought, I believe it is the duty of a health care company to prioritize their responsibility with age. Today’s drug development companies participate in an unsustainable system with which they create medications. With regard to major drug development companies today, the money (in billions) that we spend for research and development produces an inverse result of effective medications. Companies such as Bristol Meyers Squib, Bayer, and Glaxo-Smith Kline rely on blockbuster drugs. The difference between blockbuster films

    Rao,  10  (such as Lawrence of Arabia) and blockbuster drugs is the effectiveness of the result. Currently we spend billions of dollars to derive a medication that works just as well as the incumbent, but has a nominally different molecular structure. The end goal is to create a blockbuster medication which stimulates many Americans to buy such a medicine, but at unaffordable prices. An example of this would be a relatively new medication called Clarinex. Clarinex is a new drug which has similar effects as its predecessor, Claritin, but has a nominally different chemical forumla. Because it is a different molecular structure than is its predecessor, the FDA requires a complete in-vitro and in-vivo trial set completed with that is proved to not only be safe but also be stronger than the placebo. I am fairly familiar with one new model that I believe will be far more effective in producing medications while maintaining a sustainable price of research and development. Currently the one of the goals that drug developers have is to create a mix of molecules that are aimed to create a blockbuster drug. The design that I would use will aim at fixing the issue, and working from the disease down to the molecules. This reduces the excess of expenditure that modern companies use to create such blockbuster drugs by using already available means which we may apply for our purpose. If we completely reform the healthcare industry, we would be able to provide drugs for masses at a far lower price. One of the key factors to start a company that works with this model is having an effective startup with sufficient funds. I believe certain graphs illustrate this point well:

Figure  6     Rao,  11 

  Figure 6 illustrates the change in NME output per dollar over time. Four of the most powerful discoveries in the last thirty years are also shown. The decline is exponential and it is the duty of my generation to change that graph from a curved “l” to a “u”. Perhaps even more interesting is the costs continue to rise despite the inverse output. Graph 1.10 illustrates such a trend:

Figure 7 

    Rao,  12 

According to the FDA, the critical path (Phases two and three) is the most

 

important part of the process. Not surprisingly, phases two and three are the two steps at which cost has skyrocketed. However, what my company must focus on is creating a sustainable system at which healthcare is affordable.

Figure  8

Graph 8 depicts the increase in dollar per NME over the last century (defined as the beginning modern age for medicine). From 1902 to 2007 the price per NME has increased by fourteen percent each year,   disregarding inflation. For a sustainable future we need to make changes by 2015, the turning point at which the industry may collapse. Currently, at our rate, we will increase

    Rao,  13  overall spending by more the five percent each year. In most cases that will result in the demise of the industry possibly creating a recession far worse than the one we are in. If we manage to maintain the same dollar per NME value as we have today, we would have a limited but available healthcare system. For us to reach a sustainable health benchmark we would need to cut down our spending by over fifty percent. To create an economically sustainable system the next generation of biotech entrepreneurs must entertain a different system. Not based on blockbuster drugs that are not far greater than the incumbent but just foster a different molecular formula. A company that focuses not on novelty but on innovation.

Scientific Model of the Product An important aspect (as I just mentioned) in the development of drugs is the innovation. With the scientific research I have presented, I believe a complete prevention and then treatment of Alzheimer’s will have to consist of: 1. Treatment of patients who are diabetic a. Insulin 2. Research of RPI-069 and similar compounds a. Retains over sixty percent of neurons and synapses b. Working with Eva Vertes

    Rao,  14  3. Developing a new Drug which is able to act as a tape for the already amyloid-beta affected synapses and neurons a. Working with Greg Petsko 4. Consistent, but moderate, provision of caffeine and Omega-three 5. Incentives to those who exercise 6. Working on promoting PE reform 7. Prioritizing healthcare 8. Biomarkers using PIB (Pittsburgh Compound B) a. Working with researchers at Washington University in St. Louis. 9. Working with the government to help the insurance companies I believe these nine steps, both medical and public health related, will either help prevent the incidence of Alzheimer’s or work on controlling the prevalence of the disease. (Incidence and Prevalence are the two major aspects of disease control).

Management Model of the Company I believe a strong startup should have five to six crucial people who belong to the company; it is a given that everyone has sufficient knowledge of the subject at hand. 1. Chief Executive Officer: Runs the company, recruitment, and the final operations 2. Chief Operational Officer: In charge of operations and finances 3. Vice President: Has a strong understanding of field, works with clinical studies

    Rao,  15  4. Chief Scientist: Has unprecedented knowledge of the subject and a very strong professional in science a. May have (depending on money) a few research scientists under him, not always under the name of the startup 5. Communications Manager: As startups to not have all the facilities to manage clinical studies, the company needs a person to arrange this, keep the track of the schedule, demonstrate a strong knowledge in the field Angel Investors and Venture Capitalists, people who have significant net worth or capital and are willing to invest in the company are important to maintain general functions and salary. I believe those are the six components that may translate to a strong startup. With this team I would run the company such that we understand the core of Alzheimer’s while working back to the molecular design of the medication. Running a startup would require sacrifices on everyone’s part. Our main strategy to retain qualified professionals for each of the positions would be the tremendous, long-term payout. One of the most beneficial aspects to this employment design is the ability to work long distance. The Internet and communication services in today’s world allow everyone to communicate from distance. The requirement to be together in one working facility becomes more prominent after the deal with the medicine “clicks”. Like all startups a key component of the model is the ability to pay. While a medicine so revolutionary as a treatment for Alzheimer’s will need minimal marketing after launch (word of mouth and certain commercials) it is even more crucial for the company to sustain itself through investors. As the model of the company is

    Rao,  16  revolutionary, we will need a strong marketing system with which we can attain proper funding to create a strong system that can properly conduct a systematic set of clinical trials. One of the biggest differences from the approach that I hope to take from conventional methods is the comprehensive study of the disease. Today, many companies focus solely on the cure because if the overall incidence/prevalence of the disease is minimal, the profits for the companies are also minimal. To counter this I hope to work with insurance companies, the beneficiaries of this comprehensive transaction. The end goal is to have a positive impact on society while providing a reason for the employees to work. The employees will be able to participate in a great experience which not only changes the way the world thinks about medicine but also allows them to work with some of the world’s most eminent scientists. What makes this company different (and sustainable) is not only the impact we hope to have on society, but the innovative and efficient means with which we do so.