Clinical Research In India
As we try and understand Alzheimer’s better to go on to be able to treat it better, new research suggests that reclassifying it as six different subgroups could be one useful way forward – so that each type of case can then be targeted and treated differently.
It may sound like a familiar approach, given it was put forward for type 2 diabetes earlier this year. The reasoning is that not all forms of a disease have the same characteristics or need the same treatment.
Right now Alzheimer’s is usually classified as either early-onset Alzheimer’s or late-onset Alzheimer’s, but the new study says that extra categories would mean we get clearer results when it comes to drug testing and future research into the disease.
In other words, rather than treatments being discounted because they don’t work across all Alzheimer’s patients, they might be found to be very effective in specific cases.
“Alzheimer’s, like breast cancer, is not one disease,” says one of the team behind the study, Shubhabrata Mukherjee from the University of Washington School of Medicine.
“I think a good drug might fail in a clinical trial because not all the subjects have the same kind of Alzheimer’s.”
To test the hypothesis, the researchers looked at 4,050 patients with late-onset Alzheimer’s and split them into six groups, based on their cognitive functioning at the time they were diagnosed.
Cognitive scores were given in four areas: memory, executive functioning, language, and visuospatial functioning. As the participants came from five different, earlier studies, the test scores had to be standardised before patterns could be teased out.
But patterns did indeed appear: those in the largest of the six groups (39 percent of patients) had scores in all four areas that were fairly close. Those in the second-largest group (27 percent of patients) had memory scores substantially lower than the other scores.
Three of the other groups could be identified by low language scores, low visuospatial functioning scores, or low executive functioning scores compared with the other categories. The final group, 6 percent of patients, had substantially lower scores in two of the four cognitive areas.
The groups were also analysed to find genetic variations between them that might help explain the scoring patterns. A total of 33 SNPs – single nucleotide polymorphisms, or specific locations on the genome – were found to have strong genetic associations with certain subgroups.
That’s a solid step up from the 20 or so SNPs already linked to Alzheimer’s as a whole (without any subgroups).
One gene variant in particular, the APOE e4 allele, looks like being a strong risk factor for developing Alzheimer’s for people with European ancestry – something previous research has suggested – though the team was keen to point out that many people with the allele never develop Alzheimer’s at all.
And the researchers themselves say this is only the start of thinking about how we could split Alzheimer’s up into more types. The study included several thousand people, but they were all well-educated and European, for example, which is one limitation here.
Nevertheless there’s enough in the findings to suggest that we could benefit from distinguishing between categories of Alzheimer’s in this way, and from there finding more accurate ways to spot it developing and – one day, let’s hope – to come up with a cure.
“The implications are exciting,” says one of the researchers, Paul Crane from the University of Washington School of Medicine. “We have found substantial biological differences among cognitively defined subgroups of Alzheimer’s patients.”
The research has been published in Molecular Psychiatry.
With an aim to empower people to personalize their health checkups and make informed lifestyle choices that can subsequently delay/prevent the onset of diseases, Indus Health Plus, a pioneer in the preventive healthcare sector, is planning to invest Rs.75 crore over next 3-4 years to expand its personal genetic testing, DNAwise to half a million population pan India.
A majority of the fund will be used to create awareness among people about importance of personalized genetic testing in preventive healthcare. A portion of the fund will be used for technology advancement and human resource development, said Amol Naikawadi, joint managing director, Indus Health Plus.
The healthcare firm has launched DNAwise in Mumbai on December 11 at a cost of Rs.2 crore. Based on Illumina’s global screening array technology, DNAwise is a personal genetic test that decodes 7 lakh markers in the genetic makeup and generates a report after 4-6 weeks through which one can understand the health risks & personalize diet and fitness according to what suits them the best.
DNAwise is designed for all age groups and has 60 parameters related to health, nutrition and fitness. The package is available pan India, at Rs.14,999+GST and includes saliva sample kit delivered at one’s doorstep, report and telephonic counseling by a qualified genetic counselor.
Country like India where 55.4% deaths are due to non communicable diseases (NCDs). Personalised genetic test which helps identify risk factors for NCDs in advance plays a crucial role in controlling NCD deaths, said Naikawadi.
The growing number of lifestyle diseases, irrespective of the age groups, stimulated us to create this unique platform of prevention. In an endeavor to create healthy future for individuals by expanding the umbrella of prevention, we have come up with DNAwise, he added.
DNAwise analyses the health risks and food & fitness traits on the basis of one’s genetics. Knowing the genetic predispositions to various diseases helps an individual to delay/prevent the onset of diseases by modifying lifestyle. Healthy lifestyle attenuates genetic risk for diseases, he added.
DNAwise is once-in-a-lifetime investment for health that is recommended for all family members to know the predisposition of diseases, followed by yearly health examination. The genetic test report can be the guide for one’s lifelong wellness. A successful pilot project of DNAwise genetic test was conducted recently across 17 Indian cities covering 3,000 people. It was accepted very well amongst the consumers and they are now taking it for their family members, said joint managing director of Indus Health Plus.
With 18 years’ experience in preventive healthcare segment, Indus Health Plus has clocked a revenue of Rs.100 for fiscal 2017-18. The healthcare company aims to become a leader in personalized genetic test segment in less than a year.
The company has touched lives 6 lakh families and enabled them to live better through its comprehensive healthcare and wellness packages available at 122 centres in 78 cities pan India.
Without T-cells, the cells responsible for fighting off foreign cells, we humans are pretty vulnerable to disease. The T-cells themselves however rely on immune system sentinels, dendritic cells, to seek our and flag anything suspicious.
In cancer treatments like immunotherapy, this process is manipulated to get our own bodies to attack cancerous cells.
Now, for the first time, a research team from Lund University in Sweden has developed a process for converting human skin cells into these immune system sentinels, which could lead to safer immunotherapy treatment options.
Fighting cancer with the body’s own immune system is no easy task. Sometimes cancer may cause the dendritic cells to behave in unusual ways and not function properly.
There’s also the chance your body might reject the treatment all together.
By creating immune cells from a patient’s own body the chance of rejection is drastically reduced.
This process, called direct reprogramming, was recently published in the journal Science Immunology and is not only effective, but fast as well.
“From a tissue section taken from the skin, we can cultivate millions of cells and reprogram them to dendritic cells in a process that takes only nine days”, said Filipe Pereira, the leader of the research team that conducted the study.
Not only are the reprogrammed cells able to alert the body’s immune system to cancerous cells, they can also be guided by researchers to seek out specific targets before they are introduced into the body.
Cellular immunotherapy is a relatively new treatment option for fighting cancer.
Better understanding the intricacies of how our immune systems function can help us to keep healthy longer.
The research conducted by Pereira and team will help to improve treatment options and open new avenues of immunotherapy research.
In order to assess the potential of investment for medical device park at Multi-Model International Cargo Hub and Airport (MIHAN) at Nagpur, the Maharashtra Airport Development Company Ltd (MADC) has appointed an agency to come out with a detailed project report (DPR) on developing a medical device park based on a cluster based approach.
As per the cluster approach, the DPR will outline framework to set up common facilities for testing and manufacturing competencies on par with country’s first medical device park – Andhra Pradesh Med Tech Zone (AMTZ) at Visakhapatnam. MADC is also in the process of earmarking the land, land rates and formulating policies on the same, according to an official associated with the development.
Setting up of a medical device park at MIHAN, Nagpur has been deliberated over the past few months comprehensively between MADC and medical device associations.
Many companies have shown interest in both Special Economic Zone (SEZ) and non-SEZ areas of MIHAN based on the discussion between Maharashtra Chief Minister Devendra Fadnavis and Union Minister for Road Transport, Highways and Shipping Nitin Gadkari for developing bulk drugs and medical devices park at MIHAN through a collaborative approach.
Both the ministers have discussed modalities and explored areas of investment for setting up common facilities of manufacturing and testing in consultation with the industry. Subsequent to which, Maharashtra Food and Drug Administration (FDA) also held talks with companies in Nashik, Aurangabad, Mumbai, Pune and Thane to explore investment opportunities for developing pharma and medical device hub at MIHAN multi-product SEZ.
MIHAN will have dedicated zones for bulk drugs park and medical devices park along with certain benefits for setting up their units in the project as a part of its policy of ease of doing business. According to officials, 1,000 acres of land in MIHAN SEZ is likely to be developed for API production, which will boost exports and deemed exports.
These ongoing developments which are also in the interest of domestic industry is supplemented by the coming up of institutions like All India Institute of Medical Sciences (AIIMS) in the coming years and Indo UK Medicity at MIHAN. This will also pave the way for development of pharma and life sciences cluster in the country.
The Indo-UK medicity currently being run in coordination with King’s College London for treating foreign patients is aimed at giving boost to medical tourism also which will bring in foreign investments.
The multi product Special Economic Zone in MIHAN is sought to be developed for both API, formulations and a medical device park. These units will have the benefits of duty free import or domestic procurement of goods for development, operation and maintenance of SEZ units, 100% income tax exemption on export income for SEZ units for the first 5 years, 50% for the next 5 years thereafter and 50% of the ploughed back export profit for the next 5 years, external commercial borrowing (ECB) by SEZ units up to US$ 500 million in a year without any maturity restriction through recognized banking channels, exemption from central sales tax, exemption from service tax, single window clearance for central and state level approvals, exemption from state sales tax and other levies as extended by the state government and 100% FDI is being allowed.
Wasps are dangerous little insects. They’re aggressive as heck, and being stung can be on a spectrum from incredibly painful to fatal.
But that venom isn’t just dangerous to humans. It can also wipe out bacteria – and scientists have just figured out how to retain the bacteria-killing part while removing the pesky “dangerous to humans” part.
The result? A potential new antibiotic based on a peptide in wasp venom that kills bacteria without harming human cells – although we need to note that so far the only living beings it’s been tested on were mice.
“We’ve repurposed a toxic molecule into one that is a viable molecule to treat infections,” said microbiologist and immunologist Cesar de la Fuente-Nunez of MIT. “By systematically analysing the structure and function of these peptides, we’ve been able to tune their properties and activity.”
All classes of life on the planet produce antimicrobial peptides – a short chain of amino acids that kills microbes by disrupting their cell membranes – as part of their defence against infection.
As more and more bacteria develop antibiotic resistance around the world, more and more people are dying. One potential way of fighting these “superbugs” is developing a new class of antibiotics to which the bacteria have no resistance.
This is why scientists are working on trying to adapt antimicrobial peptides into antibiotics. But it’s complicated work.
The research team discovered a potential target in one particular peptide, found in the venom of a South American wasp called Polybia paulista(the same wasp whose venom was being investigated as a cancer treatment a few years ago), and consisting of just 12 amino acids.
“It’s a small enough peptide that you can try to mutate as many amino acid residues as possible to try to figure out how each building block is contributing to antimicrobial activity and toxicity,” said de la Fuente-Nunez.
First, the team developed a few dozen variants of the peptide, and tested them against 7 species of bacteria and 2 fungi to test how well they interacted with the cell membranes.
Based on this, the researchers could work out which structures and physicochemical properties of the peptides were the most effective against microbes, and refine them accordingly.
The refined peptides were tested for toxicity to humans on lab-grown human embryonic kidney cells. This way, the team established a human-safe dose level.
Finally, the peptides were ready for testing on live animals – mice. These were infected with an antibiotic-resistant bacteria called Pseudomonas aeruginosa, which is particularly dangerous to patients with compromised immune systems.
The team tested several of the most promising peptides, with varying degrees of success. Several of them did in fact reduce the level of infection. But one really stood out – at a high enough dose, it completely eradicated P. aeruginosa.
“After four days, that compound can completely clear the infection, and that was quite surprising and exciting because we don’t typically see that with other experimental antimicrobials or other antibiotics that we’ve tested in the past with this particular mouse model,” said de la Fuente-Nunez.
The research does need further work – the researchers are trying to figure out if they can retain its efficacy at lower (safer) doses.
But it’s promising. Scientists have developed a number of drugs based on antimicrobial peptides that are currently in clinical use to treat antibiotic-resistant infections – although it’s worth noting that not all such pharmaceuticals pass clinical trials.
However, even if the wasp venom ends up being a dead end, the researchers believe that the methods they developed can be applied to other antimicrobial peptides in the search for a wider range of solutions – and that’s something we all need.
The research has been published in the journal Communications Biology.