Early preclinical data suggests that there is #crosstalkbetweendiabetesandParkinsonsdisease (PD) as PD is characterized by the #deathofdopamineproducingneurons (DAergic neurons), which also happen to express high levels of #insulinreceptor on their plasma membrane. The high density of insulin receptors may cause the DAergic neurons to be sensitive to #aberrationsintheinsulinsignalingpathways. Therefore, an aberrant insulin signaling leading to the death of the DAergic neurons might be the root cause of PD. The full mechanism behind this phenomenon is not exactly clear, but it is agreed that some sort of a connection exists. It is also known that individuals with #Type2diabetes (T2D) are three-times more likely to develop PD than those without T2D, and that# insulinsignalingisdesensitized in the brains of PD patients.

#Glucagonlikepeptide1(GLP1)receptoragonists are popular medications for #T2Dtreatment, second only to insulin in popularity. These drugs work by stimulating the GLP-1 receptors in the pancreas and triggering #insulinreleasefromthepancreas. Since, these receptors have also been identified in the brain, GLP-1 receptor agonists were also thought to play a role in the #treatmentofPD. Recent findings published in #Nature demonstrated that GLP-1 analogues can #reducethesymptomsofPD and may even #preventPDprogression in #preclinicalmodels.

Therefore, if early clinical data is positive, companies with GLP-1 drugs such as AstraZeneca, Eli Lilly, Novo Nordisk, and Sanofi could soon get involved in the PD fray. As of today, none of these companies have a foothold in the PD market.

Eli Lilly’s #Trulicity and Novo Nordisk’s #Victoza are the #marketleadersinGLP1agonistmarket. In 2017, Victoza raked in about $3.6 billion (almost 50% market share), and Trulicity brought in just over $2 billion. Sanofi also has a GLP-1 agonsit drug in the market- #Exenetide.

Now, the problem statement- GLP-1 analogues can’t easily cross the blood/brain barrier (BBB); some like Trulicity do not cross the BBB at all. Therefore, prescribing a diabetes drug to PD patients on a large scale is still a long way off.

Newer formulations such as, an extended release version of Bydureon have been engineered to cross the BBB easily. The #extendedreleaseformofBydureon sustained in the blood for a duration of over 20 days. Rats models of PD, exhibited #markedimprovedinmovement in addition to enhanced #dopamineproduction over these 20 days.

#Drugdosage issues complicate the issue further. The proper dose of a GLP-analogue for a PD patient would be different from that of a diabetic; so medical professionals can’t just prescribe a diabetes drug off the hat without risking serious problems. Therefore, a whole new series of #clinicaltrials would be required, taking up a lot of time.

At this point in time, it seems that AstraZeneca might be the front runner in the race to develop a PD drug, as the extended release formulation of Bydureon has already been tested in rats. Whereas, Eli Lilly might be in for a challenge as Trulicity, cannot cross the BBB.

The key to the successful repurposing of GLP-1 analogues to treat PD therefore, lies in: (a) developing novel formulations to enable the drugs to cross the BBB, and (b) identifying the correct dosage.

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