Review of Genetic and Gene Therapy for Parkinson’s Disease

[Farooqji]

vFollowing Alzheimer's, PD has the highest number of neuronal degeneration among all neurodegenerative disorders. Deficiency of dopamine in the basal ganglia precedents motor symptoms, viz, later postural unsteadiness, rigidity, tremor, and bradykinesia. PD in most cases is instigated by an amalgamation of genetic and environmental risk components. PD is assumed to be multifactorial rather than the pathogenesis of a single definite cause. Findings from numerous disease-causing genes and genetic risk factors have validated genetic involvement in studying the pathophysiology of PD. Data obtained from linkage analyses and association studies data analyses have shown the association of various loci (EIF4G1, PARK13, PARK15, and PARK1) and several risk factors (HLA, GAK, MAPT, BST1, PARK16, GBA, LRRK2, and SNCA), respectively. A mutation of SNCA is responsible for autosomal dominant PD. The principal unit of Lewy bodies and Lewy neurites is the protein alpha-synuclein, which is coded by the gene SNCA. This protein, alpha-synuclein, possibly helps with brain plasticity and binding to synaptic vesicles. Autosomal dominant PD is also triggered by a mutation in the LRRK2 gene. Proteins translated by LRRK2 are suggestive of a function in intracellular signaling pathways. Autosomal recessive PD is instigated by transmutation in the PARK2 (Parkin) gene. The protein Parkin belongs to ubiquitin E3 ligases. Patients with Parkin mutations tend to develop motor variations and dyskinesias in the initial sequence of treatment of levodopa-responsive PD. Autosomal recessive PD is also caused by a mutation in the PINK1 gene. The mutation in this gene impairs the function of the protein leading to the rare case of early onset of Parkinson's with early onset of dementia. Mutation in DJ1 is yet rare and another cause for the causation of autosomal recessive PD. Genetic risk factors in connection with Gaucher to PD with association GBA gene. Under treatment, the primary and major treatment is to be done with levodopa preparations. Levodopa preparations give adverse effects with increased titer doses. In combination with levodopa, MAO-B inhibitors and anticholinergics are also given depending on the symptoms of the disease. Gene therapy is replacing, silencing, or correcting bad DNA with good DNA. Gene therapy is classified under disease-modifying targets and non-disease-modifying targets. Disease-modifying targets such as treatment with GDNF genes and non-disease-modifying targets such as treatment with TH, AADC, and GCH genes among others.

cureus.com/articles/117483-...

[Baca]

Farooqji, do you think gastroparesis accompanied with Parkinson’s can be helped with regenerative procedures?

[Boscoejean in reply to Baca]

Acupuncture

Acupuncture is an effective way to deal with nausea and has long been used in traditional medicine. Studies show electroacupuncture can stimulate the vagus nerve and improve the ability of the stomach to empty.

Supplements

Under medical guidance, replacing acid (betaine HCl or apple cider vinegar) and enzymes such as papain or bromelain extracts and stimulation of digestion with bitters may help improve digestion for some with gastroparesis.

Ginger is a natural prokinetic that helps improve stomach emptying to relieve nausea.

Other herbal prokinetic combinations such as bitter candytuft, angelica root, chamomile, and caraway, commonly found in the herbal formula Iberogast, have also improved dysmotility by helping the stomach muscles function appropriately.

[Boscoejean in reply to Baca]

Strengthen the Vagus Nerve

Depending on the cause of damage or dysfunction, some exercises can strengthen the function of the vagus nerve.

Humming

Yogic breathing/pranayama (particularly Alternate Nostril Breath)

Slow, deep, controlled breathing

Gargling

Singing

Yoga

Visceral manipulation-massage that aims to stimulate the vagus nerve and release tension from abdominal organs

[Zardoz]

Has anyone been following progress of any genetic treatment for Parkinson"s? Are there any trials?