BioWorld Today Columnist

Ever wonder why public school budgets are stuffed with special education expenses? Ever noticed that colleagues and friends (or maybe you) are struggling with family members facing serious challenges from learning disabilities or psychiatric illness? And what's with all the consumer ads for depression and bipolar medications in magazines?

It's not your imagination. We are seeing an explosion in the number of people with brain disorders - and not just because of better diagnoses. Neurological diseases are at the final frontier of our industry's drive to understand, treat and cure.

As a banker friend of mine said after attending a board meeting, "These meetings remind me that we have technology to fix hair, teeth, skin, bodies, but we can't fix the brain."

Biotech has given us many tools to pick apart what happens at the cellular and molecular levels in even the toughest diseases. It's time to aim this amazing machinery at the brain. Researchers have made little progress to date in finding the psychiatric equivalent of the Her-2/neu receptor to guide targeted treatment.

The fancy new-generation psychiatric drugs that were thought to provide significant improvement and reduced side effects recently were shown to be no better than the older and cheaper drugs for many patients.

That $10 billion we spent annually in the U.S. on antipsychotics isn't generating nearly that amount in benefit - partly because they are aimed at the same non-specific targets as the old medications. The biopharma industry does not have enough to say about serious childhood brain disorders.

The Ultimate Pharmacogenomic Puzzle

Today's psych drugs do not work particularly well outside of a small patient subpopulation that can't be identified ahead of time. These drugs often have unpleasant side effects, including significant weight gain, diabetes, sedation, tremors, agitation and suicide risk.

Most of these diseases are like other multi-factoral diseases, such as cardiovascular disease or cancers, in which patients with similar phenotypes might have wildly variant genetic backgrounds and environmental factors that affect cause of disease and the patient's ability to respond to specific treatments.

In some cases, like autism, the spectrum of symptoms overlaps with traits seen in the general population, making identification of patients prior to a major clinical event impossible.

The wide range of brain diseases are the ultimate pharmacogenomics puzzle. Only through large, multidisciplinary team assault do we have a prayer of finding out how to diagnose and design patient-specific treatments.

We don't have any biomarkers that allow doctors to definitively diagnose and design an effective treatment program. Treatment is "trial and error" - trying to find one drug that has more benefit for the patient than adverse effects is both time-consuming and frustrating. None of those drugs cure any of the diseases, and they have unpredictable and wildly variant therapeutic effects in different patients. (Not to mention that patients usually require therapy with medication, and finding the right therapist who accepts new patients is its own challenge.)

Finding an effective treatment doesn't mean the patient will stay on it. The nasty side effects, coupled with the fact that patients often cannot perceive their own illness or see it as a stigma, make compliance a problem. And as soon as blood levels of medication drop, the patient can be out on the streets, as ill as before.

Huge Social, Business Costs

Brain diseases affect the very core of who we are. The brain is our filter, used to create a model of the world around us that allows us to successfully interact with others. When that model becomes faulty, the mentally ill person can't contribute to society and increasingly relies on society's care.

The National Alliance on Mental Illness (NAMI) estimates the economic cost of untreated mental illness at $100 billion annually in the U.S. alone.

For many adult American patients, the care they receive often is the police picking them up and taking them to the nearest county hospital for a 72-hour hold.

Patients are dumped back out on the streets with a prescription in their hands and told to go to a clinic. They return to the hospital when their behavior again generates a police report. According to data from the U.S. Department of Justice, 64 percent of local inmates, 56 percent of state prisoners and 45 percent of federal prisoners have symptoms of serious mental illness.

One of the most frightening aspects is the impact on our future. NAMI says that the most serious and disabling conditions, often surfacing in the prime of life, affect up to 10 million adults and up to 5 million children in the U.S.

Another NAMI survey found that one in three college students experience prolonged depression, one in four consider suicide, and one in seven are seriously affected in their scholastic activities. And a recent report on campus mental health issues at the University of California detailed a dramatic growth in suicide attempts and serious mental illness coinciding with a significant cut in funding for services to care for these students.

Science, Money Can Solve This

While it's a daunting task, it's not hopeless. In the recent issue of Nature Neuroscience, papers discussed the focus on establishing pathways between genetic variation and behavioral disorders. One study examined the role of NMDA receptors in memory activation with an eye to therapeutic manipulation. The team treated memory as just another biological reaction, like receptor turnover, that could be manipulated in a very targeted way.

It will require major, multidisciplinary, collaborative research to figure out the complex relationships between gene function and mutation, environmental factors and the added challenge of understanding the dichotomy of the mind vs. the physical brain.

Brain research will require us to give up our comfortable, concrete way of thinking about biology. Numerous recent peer-reviewed studies have shown very clear connections between our ability to think about something and generate physical change within our bodies.

To fund the war on brain disease, we need a new March of Dimes - that federal foundation formed in 1938 by President F. Roosevelt to fight polio. That agency's fund raising supported creation of effective polio vaccines, then shifted its focus to preventing birth defects and infant mortality by supporting early genetics research. Today, $30 million is provided annually around the world, filling that research-to-clinic gap.

Funding that gap for brain research got a big boost this fall when the Allen Institute for Brain Research introduced a computerized atlas showing expression of the 20,000 genes that operate in the mouse brain with all kinds of snazzy bells and whistles. That tool will help support the multidisciplinary work required ( Paul Allen, cofounder of Microsoft, created the institute in 2003 with $100 million in seed money.

It's time for some of those who made big bucks in biotech to follow suit.

A growing number of biopharma companies are working on novel, targeted drugs for cognition, schizophrenia, depression and anxiety, but they need better information for success. Treatments that provide unequivocal, targeted benefit without nasty side effects, coupled with true diagnostic tools will revolutionize care for these patients and drive reimbursement.

Science is giving us tools to meet these goals in the foreseeable future. We declared war on cancer in the 1970s and look at the progress we have made. This is a market opportunity that can't be ignored, and we are the ones with the tools, the resources, and the focus to do it.

Robbins-Roth, Ph.D., founding partner of BioVenture Consultants, can be reached at Her opinions do not necessarily reflect those of BioWorld Today.

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