Why researchers are turning to lithium

• There are about 32 million individuals globally dwelling with Alzheimer’s illness, with that quantity anticipated to hit 152 million by 2050.
• Whereas there are some medicines for Alzheimer’s illness, they’re solely used within the earliest phases to assist sluggish cognitive decline or at extra superior phases to deal with widespread illness signs.
• A new examine makes the case for treating Alzheimer’s illness with low-dose lithium because the drug helps to counter neuroprogression and supplies neuroprotective advantages.

Researchers additionally consider the quantity of individuals worldwide dwelling with Alzheimer’s illness and associated dementias will hit 152 million by 2050.

There’s at present no treatment for Alzheimer’s illness. Whereas there are some medications accessible, they’re solely used within the earliest phases to assist sluggish cognitive decline or at extra advanced stages to deal with widespread signs of the situation.

“Alzheimer’s illness and different dementias are devastating situations for people, households, and society at giant,” Husseini K Manji, MD, FRCPC, professor at each Oxford College in the UK and at Yale College in the USA, co-chair of the U.Okay. Authorities Psychological Well being Targets Program (previously MH Mission), instructed Medical Information As we speak.

“Regardless of latest advances in monoclonal antibodies, Alzheimer’s illness and different dementias stay an enormous and rising world public well being disaster. Present therapies largely deal with single pathologies, reminiscent of eradicating amyloid plaques, however Alzheimer’s is extremely advanced and entails a progressive cascade of mobile vulnerabilities, together with mitochondrial decay, oxidative stress, and lack of synaptic connections,” Manji defined.

He’s the lead creator of a brand new examine printed within the journal JAMA Psychiatry making the case for treating Alzheimer’s illness with low-dose lithium — a medicine used to deal with bipolar disorder — because the drug helps to counter neuroprogression and supplies neuroprotective advantages.

Over the past 25 years, Manji defined, a convergence of molecular, imaging, and epidemiological information from research conducted in his lab and others, has proven that lithium is rather more than only a psychiatric drug — it possesses main neurotrophic and neuroprotective properties.

“Nonetheless, conventional psychiatric doses of lithium carbonate are sometimes poorly tolerated by older people resulting from a high adverse effect burden, notably dangers to kidney and thyroid operate,” he continued.

“My lab, due to this fact, did plenty of research with low-dose lithium to point out that most of the neurotrophic and neuroprotective properties are seen at significantly decrease doses/ranges than these historically utilized in bipolar dysfunction,” Manji instructed us.

“These findings have been replicated by different unbiased laboratories,” he famous. “Thus, low-dose lithium might exert neurotrophic results however have significantly fewer unwanted side effects.”

On this examine, Manji and his staff clarify that low-dose lithium is just not solely a temper stabilizer, but in addition helps to counter mind adjustments generally known as neuroprogression.

“In bipolar dysfunction, neuroprogression refers back to the manner repeated temper episodes trigger cumulative, structural injury, and shrinkage in key mind areas over time,” he detailed.

“Lithium is exclusive as a result of it will possibly really protect and even reverse this mind shrinkage. We consider low-dose lithium can counter an analogous progressive decline in Alzheimer’s illness. Lithium exerts results on main neurotrophic cascades — particularly BDNF, bcl-2, and GSK-3 — which might be postulated to attenuate illness development; these findings have been replicated quite a few occasions by unbiased labs.”

– Husseini Okay Manji, MD, FRCPC

“Moreover, in people, lithium remedy has been proven to reverse illness-related neurotrophic deficits in bipolar dysfunction,” Manji added. “Though the illnesses are distinct, lithium impacts very basic mobile neurotrophic processes, which might be relevant to Alzheimer’s illness as properly.”

The examine additionally experiences that low-dose lithium might present neuroprotective advantages.

Manji defined that reasonably than simply making an attempt to wash up a single poisonous protein, low-dose lithium acts like a grasp change that upgrades the mind’s total mobile protection system by turning up the manufacturing of BDNF, blocking the exercise of deleterious enzymes, and enhancing mind energetics.

In brief, he mentioned, lithium helps susceptible mind cells survive and keep wholesome regardless of the poisonous setting of Alzheimer’s.

“Seventy-five years after reworking psychiatric care, lithium is on the forefront of a brand new frontier as a strong, multi-targeted intervention able to slowing development in early dementia,” Manji added.

“By shifting our focus to low-dose methods, we will harness its strong neuroprotective capabilities safely, opening the door to an accessible, low-cost weapon within the world struggle towards Alzheimer’s illness,” he instructed us.

MNT had the chance to talk with Laura Nisenbaum, PhD, government director of drug growth for the Alzheimer’s Drug Discovery Basis (ADDF) — who was not concerned on this analysis — about this examine.

Nisenbaum mentioned her first response to the examine was considered one of real curiosity, and what makes this evaluate compelling is that so many unbiased traces of proof are pointing in the identical course.

“The sphere has been asking questions on lithium for years, and this evaluate synthesizes greater than 2 a long time of analysis and presents a case for additional exploration of lithium to find out if it’s a possible disease-modifying remedy, reasonably than merely a repurposed psychiatric medicine,” she defined.

“The breadth of organic rationale can be intriguing. Lithium seems to behave on a number of organic processes central to Alzheimer’s, together with protein clearance, mitochondrial operate, and tau pathology. That multi-target profile is important as a result of Alzheimer’s is just not a single-pathway illness,” Nisenbaum detailed.

Nisenbaum careworn it was it is crucial for researchers to proceed to seek out new potential remedy choices for Alzheimer’s illness and different varieties of dementia.

“The remedies accessible at the moment supply significant progress, however they go away loads on the desk,” she defined. “There’s a actual alternative to deliver new remedies ahead, whether or not together with current therapies or by means of a precision drugs method, the way in which we now deal with most cancers, matching the correct remedy to the correct affected person on the proper time.”

“Repurposed medicine like lithium are value taking severely in that context,” Nisenbaum continued. “Lithium has an extended scientific historical past, a well-understood security profile at low doses, and a price and accessibility profile that might make it viable at scale globally.“

“Figuring out established therapies that focus on the underlying biology of Alzheimer’s and may realistically attain broad populations is a vital avenue for the sector to discover,” she mentioned.

Lastly, MNT additionally spoke to Dung Trinh, MD, internist for the MemorialCare Medical Group and chief medical officer of the Wholesome Mind Clinic in Irvine, CA, about this examine.

Trinh, who was not concerned within the analysis, commented that his first response was considered one of cautious optimism.

“This evaluate raises an intriguing chance that low-dose lithium may have an effect on a number of organic pathways concerned in neurodegeneration, together with neuronal survival, irritation, oxidative stress, mitochondrial operate, and tau biology,” he, defined.

“That mentioned, this isn’t but a practice-changing discovering,” he cautioned. “As a clinician, I might not suggest that sufferers begin lithium on their very own, particularly as a result of lithium can have an effect on kidney and thyroid operate and should work together with different medicines.”

“The examine is finest considered as a powerful rationale for rigorous scientific trials, not as proof that lithium must be used routinely for Alzheimer’s prevention or remedy,” Trinh instructed us.

“The subsequent step must be a well-designed randomized, placebo-controlled scientific trial in individuals with biomarker-confirmed gentle cognitive impairment or early Alzheimer’s illness. Researchers ought to clearly outline the lithium formulation, dose, length, blood-level targets, and safety-monitoring plan, particularly for kidney and thyroid operate. I might additionally prefer to see outcomes that transcend reminiscence testing, together with biomarkers of amyloid, tau, neurodegeneration, MRI changes, each day operate, caregiver-reported outcomes, and high quality of life. The important thing query is whether or not low-dose lithium can present significant mind advantages whereas remaining protected sufficient for older adults over time.”