Pharmacological treatment and the prospect of pharmacogenetics in Parkinson’s disease

Abstract

Summary Parkinson disease (PD) is a progressive movement disorder marked by tremor, rigidity, bradykinesia and postural instability. Levodopa (l‐dopa), usually combined with a peripheral dopa decarboxylase inhibitor, has been proved to provide the best symptomatic benefit for PD. However, its long‐term efficacy is limited because of motor complications and drug‐induced dyskinesia. Dopamine agonists, catechol‐O‐methyltransferase inhibitors and monoamine oxidase‐B inhibitors are anti‐parkinsonian (anti‐PD) drugs that have been found to further improve the potency of l‐dopa and prevent the onset of motor complications. However, as PD is a progressive disorder, all the drugs used for its therapy, manifest reduced efficacy and adverse effects with time. Research on the field of pharmacogenetics has pointed out that the genetic variability of each individual determines to a large extent the inter‐individual variability in response to anti‐PD drugs. Clinicogenetic trials show that drug efficacy or toxicity or susceptibility to side effects are features governed by genetic principles. This article is a review of the present pharmacological treatment of PD and current pharmacogenetic data for PD.

Risk factors and predictors of levodopa-induced dyskinesia among multiethnic Malaysians with Parkinson's disease

“…Studies in levodopa-naïve MPTP animal models have demonstrated that higher dose and frequency of levodopa administration led to more severe and intense dyskinesia [6,7]. In addition, pharmacogenetic factors, such as polymorphisms of the catechol-o-methyl transferase gene and dopamine receptor gene, particularly the DRD2 receptor may also increase the genetic susceptibility for developing dyskinesia [8].…”

Protein Homeostasis as a Therapeutic Target for Diseases of Protein Conformation

“…Perhaps the most urgent need is for the development of therapeutic approaches to arrest, stabilize, or reverse the progression of neurodegeneration. The current use of L-dopamine (L-dopa), a precursor of dopamine, for Parkinson’s disease, to improve motor function and patient quality of life, has a limited long-term efficacy due to motor complications and drug-induced dyskinesia [13]. Likewise riluzole, the only drug approved for ALS, and the antipsychotics and neuroleptics used in Huntington’s disease only have modest beneficial effects to extend patient survival [14, 15].…”

Prolactin as a candidate sebotrop(h)ic hormone?

“…Almost a century ago, Cohn described seborrhoea as a symptom of postencephalitic Parkinson's disease . Much later, these findings were replicated in patients with both postencephalitic and idiopathic Parkinson's disease, characterised by a loss of dopaminergic neurons in the substania nigra . Interestingly, although sebum production was increased in patients with various neurological diseases, the association with seborrhoea was only statistically significant in patients with Parkinson's disease: both postencephalitic and idiopathic .…”