Future Treatments

Key Facts

  • The development of disease-slowing therapies is perhaps the most pressing goal in PD drug development.
  • Multiple substances are being explored as potential treatments of PD symptoms.

Since the 1970s levodopa has been the cornerstone of PD management. Other dopaminergic agents, anticholinergics, MAO-B inhibitors, COMT inhibitors, and amantadine have also shown efficacy in the treatment of the disease.  To date, we have a good supply of symptomatic medications that are effective for motor symptoms, but many non-motor problems in PD remain under recognized and under treated.

The development of disease-slowing therapies is perhaps the most pressing goal in PD drug development, but there is plenty of room for the development of better symptomatic therapies.

Here is the list of some agents that are currently being studied in PD:

Disease Slowing Agents

  • Creatine is being studied in a five year double-blind, placebo-controlled multicenter trial in early PD to see if it is disease-slowing;
  • Pioglitazone is being studied for PD.

Symptomatic Therapy

  • There are numerous adenosine A2A receptor antagonists (istradefylline, etc) under study in PD for amelioration of PD symptoms, and this represents a novel mechanism of action for PD meds. These medications have many potential benefits for PD including reduction of “off” time.

Improved Levodopa Delivery

  • The making of an improved delivery of levodopa would be a significant step forward, and a carbidopa/levodopa gel preparation is being studied that appears to reduce motor fluctuations and motor symptoms significantly in advanced PD patients who may not be good DBSi surgical candidates.
  • The one drawback of this therapy is that it requires wearing a pump and a PEG/PEJ tube infusion into the gut to deliver the gel.
  • Another extended release form of carbidopa/levodopa is also being developed, and this has shown promise in some early studies.  Unfortunately, it has been difficult, if not impossible, to deliver levodopa through the skin in a patch formulation, given it is not lipophilic.
  • Levodopa pumps are available in many countries but not in the US.

Non-motor Symptoms

  • While rivastigmine is approved for the treatment of PD dementia, acetylcholinesterase inhibitors leave a lot to be desired in therapy of dementia.
  • Psychosis and visual hallucinations are typically treated with quetiapine and, in rare cases, clozapine, given that these are the only antipsychotics that do not typically worsen PD motor symptoms.
  • Both of these drugs have significant issues in that (1) quetiapine can be associated with development of metabolic syndrome and may be associated with increased mortality in older patients with dementia, and (2) clozapine can cause agranulocytosis and requires routine blood monitoring.
  • Pimavanserin is a novel antipsychotic currently under study in PD for visual hallucinations and psychosis.    
References: 

Emre M, Aarsland D, Albanese A, et al.  Rivastigmine for dementia associated with Parkinson’s disease. N Engl J Med 2004;351(24):2509-2518.

Olanow CW, Stern MB, Sethi K.  The scientific and clinical basis for the treatment of Parkinson disease (2009).  Neurology. 2009;72(21 suppl 4):1S-136.  

Olanow CW, Kieburtz K.  Defining disease-modifying therapies for PD-a road map for moving forward. Mov Disord 2010; 25:1774-1779.

Zesiewicz TA, Sullivan KL, Arnulf I, et al.  Quality Standards Subcommittee of the American Academy of Neurology. Practice Parameter: treatment of non-motor symptoms of Parkinson disease: report of the Quality Standards Subcommittee of the American Academy of Neurology.  Neurology. 2010;74(11):924-931.