Scientists tested an experimental Alzheimer's drug in mice that targets neurotransmitter receptors in the brain, and may hold promise for future treatment.
In a new study, scientists have tested an experimental drug in mice that may hold promise for future Alzheimer’s treatments. The drug involves a small molecule that boosts the function of neurotransmitter (NMDA) receptors found between brain cells.
By supporting communication between brain cells, or neurons, NMDA receptors play a role in cognition and memory. Researchers have known for some time that impairment in NMDA receptors is associated with cognitive decline and amyloid buildup in Alzheimer’s patients. It’s also linked to other chronic neuropsychiatric and neurodegenerative diseases, as well as epilepsy.
Increasing activity and function in synaptic NMDA receptors through the use of this experimental drug showed it could improve memory as well as the brain’s rhythm patterns, the study concluded.
The researchers tested the drug, simply called GNE-0723 in this early stage, on mice with Alzheimer’s disease and Dravet syndrome — a rare form of epilepsy. GNE-0723 works by reducing low-frequency oscillations in the brain, a type of activity that becomes more frequent in Alzheimer’s disease and Dravet syndrome.
Reducing these oscillations led to improved cognition and memory, and even stopped epileptic activity in the mice. After being on the treatment for several weeks, the mice actually showed improvements on learning and memory tests compared to mice that were untreated.
“What we saw after the treatment were brain-wide changes in neural activity that shift the brain to a more active state that facilitates learning and memory,” Jorge Palop, Gladstone Associate Investigator and senior author of the study, said in a news release.
Though it was done in mice, the authors of the study hope it may hold potential to be further developed down the road and tested in humans.
“This is the first time we’ve explored what this type of experimental drug does in animal models,” Jesse Hanson, a scientist at Genentech and author of the study, said in the news release. “It was very gratifying to see an effect on both the brain’s electrical activity and the animals’ behavior.”
Currently, research into finding a drug to treat Alzheimer’s is divided into several different camps. Some drugs target beta-amyloid buildup, which is still considered one of the main drivers of the disease. Biogen’s aducanumab, which fights amyloid, showed promising results in recent data and is being submitted to the FDA for approval.
Other research is aiming to develop drugs that battle tau protein, inflammation or genetics that contribute to the disease. The latest study, meanwhile, may open up a pathway for a potential therapy that hones in on a specific part of the brain — NMDA receptors.
“Before now, we haven’t had ideal tools to enhance synaptic NMDA receptors,” Palop said. “Now, the ability to specifically target these receptors opens up a lot of new possibilities for treating cognitive disorders.”
Wanasayansi wametumia dawa ya Alzheimer's kwa panya, ambayo inashambulia neurotransmitter receptors katika ubongo na inaweza kuwa na ahadi kwa ajili ya matibabu ya baadaye. Katika utafiti mpya, wanasayansi wamejaribu dawa ya majaribio katika panya ambayo inaweza kuwa na ahadi kwa ajili ya matibabu ya baadaye ya Alzheimer. Dawa hiyo inahusisha molekuli ndogo ambayo huongeza kazi ya neurotransmitter (NMDA) receptors zinazopatikana kati ya seli za ubongo. Kwa kuunga mkono mawasiliano kati ya chembe za ubongo, NMDA huchangia kumbukumbu na utambuzi. Watafiti wamekuwa wakijua kwa muda kwamba udhaifu katika receptors NMDA ni kuhusishwa na kupungua kwa utambuzi na amyloid kujenga katika wagonjwa wa Alzheimer. Pia inahusishwa na magonjwa mengine ya neuropsychiatric na neurodegenerative, pamoja na kifafa. Kuongeza shughuli na kazi katika receptors synaptic NMDA kupitia matumizi ya dawa hii majaribio alionyesha inaweza kuboresha kumbukumbu kama vile mifumo ya msimu wa ubongo. Watafiti walijaribu dawa hiyo, inayoitwa GNE-0723 katika hatua hii ya mapema, kwenye panya walio na ugonjwa wa Alzheimer na ugonjwa wa Dravet - aina nadra ya kifafa. GNE-02323 hufanya kazi kwa kupunguza oscillations ya masafa ya chini katika ubongo, aina ya shughuli ambayo inakuwa mara kwa mara katika ugonjwa wa Alzheimer na Dravet syndrome. Kupunguza misukosuko hiyo kuliboresha uwezo wa kutambua na kukumbuka mambo, na hata kukomesha ugonjwa wa kifafa kwa panya. Baada ya kutumia dawa hiyo kwa wiki kadhaa, panya hao walionyesha maendeleo katika masomo na vipimo vya kumbukumbu ikilinganishwa na panya ambao hawakutiwa dawa hiyo. "Kile tulichokiona baada ya matibabu ilikuwa mabadiliko ya ubongo katika shughuli za neva ambazo hubadilisha ubongo kuwa hali ya kazi zaidi ambayo inawezesha kujifunza na kumbukumbu, ""Jorge Palop, Mtafiti Mshirika wa Gladstone na mwandishi mwandamizi wa utafiti huo, alisema katika taarifa ya habari." Ingawa utafiti huo ulifanywa kwa panya, waandishi wa utafiti huo wanatarajia kwamba huenda ikawa na uwezo wa kuendelezwa zaidi na kupimwa kwa wanadamu. "Hii ni mara ya kwanza tumekuwa kuchunguza nini aina hii ya madawa ya majaribio hufanya katika mifano ya wanyama", Jesse Hanson, mwanasayansi katika Genentech na mwandishi wa utafiti, alisema katika taarifa ya habari. <unk>Ilikuwa ya kuridhisha sana kuona athari juu ya shughuli za umeme za ubongo na tabia za wanyama.<unk> Kwa sasa, utafiti wa kupata dawa ya kutibu Alzheimer<unk>s umegawanywa katika kambi kadhaa tofauti. Dawa fulani huelekeza dawa hiyo kwenye beta-amyloid, ambayo bado inachukuliwa kuwa mojawapo ya visababishi vikuu vya ugonjwa huo. Biogen's Aduanumab, ambayo hupigana na amyloid, ilionyesha matokeo ya kuahidi katika data za hivi karibuni na inawasilishwa kwa FDA kwa idhini. Utafiti mwingine unakusudia kuendeleza dawa zinazopigana na protini ya tau, uvimbe au maumbile ambayo huchangia ugonjwa huo. Utafiti huu wa hivi karibuni unaweza kufungua njia ya tiba inayoweza kuathiri sehemu maalum ya ubongo - receptors za NMDA. "Kabla ya sasa, hatukuwa na zana bora za kuboresha receptors za NMDA za synaptic", Palop alisema. "Sasa, uwezo wa kulenga hasa receptors hizi hufungua uwezekano mwingi mpya kwa ajili ya kutibu matatizo ya utambuzi".