I am an associate research scientist in the chemistry department at Columbia University. Our lab (http://www.columbia.edu/cu/chemistry/groups/sames/
) is currently developing novel therapeutics for the treatment of depression, anxiety, and related mood disorders and we need your help!
There is a considerable and longstanding need for new approaches to depression therapy. Greater than 50% of patients do not respond, or respond poorly, to treatment with standard antidepressant drugs (e.g. SSRIs like Prozac). Similarly, the rate of onset for beneficial effects is often slow, being measured in weeks rather than hours. Further, successful management of depression with currently available drugs is often associated with significant negative side effects and reduced quality of life.
The atypical antidepressant tianeptine has been used in Europe and other countries worldwide for several decades but has never been approved in the United States. This is surprising considering that it already addresses several of the shortcomings prevalent with more commonly prescribed antidepressants. Specifically, it is effective in patients resistant to other drugs, is rapid acting, and has a reduced side effect profile. However, despite longstanding interest in this agent, its direct target, and thus its molecular mechanism of action, have remained elusive. Recently, our lab discovered that tianeptine is a mu- and delta-opioid receptor agonist and we propose that activation of one or both of these receptors is the initial event responsible for the beneficial effects of the drug. This is an exciting and unexpected discovery that casts the large body of tianeptine research in an entirely new light. Opioid receptor agonists have recently become a growing area of interest as a potential approach for depression treatment and our discovery is only likely to further advance this trend. For more information regarding our proposed mechanistic hypothesis and related literature please see our recent publication which is freely available online (http://www.nature.com/tp/journal/v4/n7/full/tp201430a.html
Knowledge of a potential molecular mechanism of action has allowed our lab to develop new analogs of tianeptine that we believe may have improved therapeutic properties. One shortcoming of tianeptine is its short duration of effects, which means that the drug must be taken three times per day. By making modifications to tianeptine's chemical structure, we hope to slow metabolic breakdown and thus develop new agents with significantly longer duration of effects. Ideally we hope to design a therapy that may be taken only once per day. Increased half life is also likely to increase the overall efficacy against depressive symptoms, as more drug is in the brain at any given time. Similarly, we are attempting to design new analogs with increased potency at their opioid receptor targets. This will allow smaller doses to be administered while still achieving the same level of beneficial effects. Reduced dosing is typically advantageous as it reduces the probability of idiosyncratic side effects.
Our lab is currently deeply involved in fundamentally understanding the molecular, cellular, and systems level signaling events mediated by tianeptine and related opioid agonists. By better understanding the fundamental science behind these processes we hope to be able to better design new drugs which are able to modulate neuronal signaling in just the right way, thereby achieving the desired therapeutic benefit. Simultaneously, we hope to translate our fundamental studies into viable drug candidates. We have already synthesized a large number of tianeptine analogs and are currently studying their therapeutic properties. To further our work we have formed a world class team of scientists with complementary expertise. The Sames Lab (where I work) has strong experience in complex molecule synthesis, molecular design, medicinal chemistry, and cell signaling biology. To add to our capabilities, we have ongoing collaborations with the laboratories of Jonathan Javitch and Rene Hen (both at Columbia University Medical Center), providing expertise in molecular pharmacology and animal behavioral models for depression/anxiety.
Unfortunately, this all costs money, A LOT of money. Decreasing availability of grant funding from federal agencies like the National Institutes of Health has made the current academic funding climate extremely competitive and uncertain. Likewise, obtaining grant funding for the translational aspects of our research (e.g. actually bringing new drugs towards the market) is even more challenging, as this is largely perceived to be the realm of industry, not academia. Accordingly, there is a large funding gap between the fundamental studies of a new potential drug carried out in an academic lab and the point at which such a compound might enter clinical trials or be further pursued as a commercial enterprise. For example, to complete the animal toxicology studies required by the FDA for a new drug candidate to enter human trials costs in the realm of $1 million. This is of course assuming everything goes perfectly, which is rarely the case with groundbreaking research. However, this does not mean small donations can't help! The expenses of a lab are varied, but all are critical. As an example, please consider a few things we will be able to do with your contributions.
$20 - This amount will allow us to buy one of the many chemicals we need to synthesize new potential drugs.
$180 - This amount will allow us to run a metabolic stability assay in liver cells to see if the test compound is likely to survive in the bloodstream.
$400 - This amount will buy us antibodies needed to study the molecular level signaling pathways activated by different receptors.
$1800 - This amount will allow us to run a pharmacokinetic study in mice. Such work tells us the actual concentrations of drug reached in the blood and brain.
These are just a few examples of how relatively modest sums can make a large contribution to our research efforts. All funds raised in this campaign will be used to directly support our research and I will provide updates on how the money is being used and the overall progress of our programs. Therefore, I hope you will consider giving us a helping hand and in turn, let us do our best to help the millions suffering from debilitating depression.