Research
Sowing the Seeds of Success( continued from cover)
through testing and toward regulatory approval.
MOTOR SYMPTOM THERAPIES
While available medications can treat many of the motor symptoms of Parkinson’ s disease, these drugs can lose effectiveness and wear off too early. MJFF supports potential new therapies to prevent or quickly relieve“ off” episodes and control motor symptoms.
One such therapy is an underthe-tongue thin film strip from Cynapsus Therapeutics. Due in part to the success of this compound in the MJFF-funded Phase II trial, Cynapsus recently announced a buyout by Sunovion Pharmaceuticals. Researchers expect to ask the U. S. Food and Drug Administration for approval in the first half of 2017, and, since the drug has received Fast Track Designation, it may move through review more quickly.
Other MJFF-supported motor therapies in testing that aim to control motor symptoms without troubling side effects include Neuroderm’ s underthe-skin delivery of levodopacarbidopa and Acorda’ s inhaled form of levodopa. MJFF’ s early investments in these compounds have helped speed their discovery and development and attracted larger investors to support their final phases of testing, bringing these important therapies closer to patients.
DISEASE-MODIFYING PHASE III TRIALS
The development of two commercially available compounds that showed promise as potential disease-modifying therapies for Parkinson’ s received initial funding from MJFF. Isradipine is a drug used to treat high blood pressure that may also prevent the death of dopamineproducing cells. Inosine is a dietary supplement that the body converts into the antioxidant urate; studies have linked higher urate levels with lower risk of PD.
Since both drugs are available on the market, there was not enough initial interest in their development to attract funding from pharmaceutical companies. The Foundation’ s support of early testing of these compounds showed that they are both safe and effective in individuals with PD. These compounds are now in Phase III testing( both trials are being funded by the National Institutes of Health), thanks in part to the Foundation’ s efforts to“ de-risk” their early development.
“ The Foundation’ s early and step-wise investment has not only helped us reach this advanced stage of testing for disease modification, the knowledge gained with its support also greatly enhances the prospects for success of the Phase III trial,” said Michael Schwarzschild, PhD, who led the Phase II trial for the inosine study.
Please note, while these compounds are available, neither has been approved for PD. Speak to your doctor before adding any supplement or medication to your treatment regimen.
THERAPY AGAINST GENETIC TARGET
Targeting the LRRK2 gene, the greatest known genetic contributor to PD, may help correct cellular dysfunction in PD. However, pre-clinical studies on drugs that block LRRK2 function raised concerns about their safety. In order to address this roadblock which could have prevented further development, MJFF organized the LRRK2 Safety Initiative, an unprecedented partnership between pharmaceutical companies( Genentech, Merck and Pfizer). Since these companies hold competitive interests in drug development, such an initiative would not have formed without MJFF’ s stewardship. The collaborative effort demonstrated that the compounds did not cause breathing problems and that the effects were reversible, meaning that these drugs could advance into further testing.
The outcomes of this initiative were cited as one reason Denali Therapeutics recently licensed LRRK2 compounds from Genentech for development, bringing these compounds one step closer to clinical testing.
“ This is a textbook example of what we exist to do: persevere to overcome issues that would otherwise set PD drug development back by years,” MJFF CEO Todd Sherer, PhD, told Forbes.
Stay tuned to our blog for updates on these studies: blog. michaeljfox. org.
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