Cure hope for Parkin­son’s suf­fer­ers

Op­ti­mism af­ter dis­cov­ery of ge­netic link to con­di­tion that af­fects Ashke­nazim


THE TREAT­MENT and un­der­stand­ing of Parkin­son’s dis­ease have evolved over the past 50 years. But the most im­por­tant dis­cov­ery — a drug that slows or stops the progress of the con­di­tion, with its symp­toms of tremor, stiff­ness and slow­ness of move­ment — has re­mained elu­sive.

Now a con­sen­sus is emerg­ing among re­searchers that a rare ge­netic con­di­tion called Gaucher dis­ease — which is more com­mon within the Ashke­nazi com­mu­nity than in the wider com­mu­nity — may hold the key.

It was in 1817 that James Parkin­son iden­ti­fied the “shak­ing palsy” that would later be re­named af­ter its dis­cov­erer. A cen­tury later, sci­en­tist Fred­er­ick Lewy ob­served through his mi­cro­scope that Parkin­son’s pa­tients’ brains showed clear dif­fer­ences from non-suf­fer­ers.

In the 1970s the emer­gence of drugs that im­proved the move­ment-re­lated symp­toms rev­o­lu­tionised the qual­ity of life for pa­tients.

It is, how­ever, within the last two dec- ades, with the de­tec­tion of a num­ber of genes that cause Parkin­son’s, that we are be­gin­ning to ap­pre­ci­ate they may lead the way to a cure.

In par­tic­u­lar, re­cent dis­cov­er­ies link­ing the gene that causes Gaucher dis­ease to Parkin­son’s has opened up new and ex­cit­ing av­enues to de­vel­op­ing pow­er­ful new treat­ments for both con­di­tions.

Gaucher was first de­scribed in 1882. It is caused by the in­her­i­tance of a faulty gene (glu­co­cere­brosi­dase, or GBA) from each par­ent, re­sult­ing in the body’s in­abil­ity to break down cell prod­ucts, which then ac­cu­mu­late in parts of the cell called lyso­somes.

The dis­ease can man­i­fest it­self in many dif­fer­ent ways. Some in­di­vid­u­als with two faulty GBA genes do not de­velop symp­toms. Most are af­fected, al­though the sever­ity may vary greatly, even within the same fam­ily.

The di­ag­no­sis is ini­tially by the pre­sen­ta­tion of symp­toms like a low blood count or en­larged spleen, fol­lowed by blood tests and ge­netic test­ing. Cur­rent treat­ments have emerged within the past 20 years and re­sulted in many af­fected pa­tients liv­ing nor­mal lives.

In the 1990s doc­tors no­ticed that some of their Gaucher pa­tients and fam­ily mem­bers were de­vel­op­ing the early signs of Parkin­son’s. While two copies of the faulty GBA gene are

Re­searchers are test­ing new drugs for both Parkin­son’s and Gaucher re­quired to de­velop Gaucher dis­ease, hav­ing one (known as car­ri­ers) or two copies in­creases the risk of Parkin­son’s. It ap­pears that within the UK, up to five to 10 per cent of Parkin­son’s pa­tients carry one copy of the ab­nor­mal GBA gene, ris­ing to 25 per cent in parts of Is­rael.

There are two goals that fol­low from the dis­cov­ery of the Gaucher-Parkin- son’s link. The first is to understand how the faulty GBA gene can cause Parkin­son’s. The sec­ond is to de­velop a drug to stop Parkin­son’s de­vel­op­ing in those who have the faulty GBA gene.

Doc­tors and sci­en­tists at the Royal Free Hos­pi­tal in Lon­don are lead­ing re­search groups from Italy, Canada, Ger­many, USA and Is­rael, us­ing sever- al ap­proaches, in­clud­ing novel stem cell tech­nol­ogy, to study the link. New drugs are al­ready be­ing tested.

Gaucher pa­tients and their fam­i­lies can play a cru­cial role. The Royal Free re­searchers are us­ing blood and tiny skin sam­ples to de­velop stem cells in or­der to study the Gaucher-Parkin­son’s link at a molec­u­lar level.

Im­por­tantly, this al­lows them to test the suc­cess of new drugs in the lab­o­ra­tory be­fore offering them to pa­tients in a clin­i­cal trial.

How­ever, more pa­tients and their fam­i­lies are needed for this vi­tal re­search, cur­rently funded by the Med­i­cal Re­search Coun­cil and the EU.

There is sig­nif­i­cant op­ti­mism that, with more help from Gaucher pa­tients and from those with Parkin­son’s, sig­nif­i­cant ad­vances to­wards new drug ther­a­pies for suf­fer­ers of both diseases can be made in a short pe­riod. This is an edited version of a Jewish Care Health Insight lec­ture given this week. Pro­fes­sor Tony Schapira is the head of the clin­i­cal neu­ro­science depart­ment at the Univer­sity Col­lege Lon­don In­sti­tute of Neu­rol­ogy. Dr Stephen Mullin is Leonard Wolf­son clin­i­cal re­search fel­low at the in­sti­tute. If you would like to par­tic­i­pate in the re­search at the Royal Free, email rap­ for de­tails

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