Alport syndrome: an interview with Dr Paul Grint, CMO, Regulus Interview conducted by April Cashin-Garbutt, BA Hons insights from industryDr http://modafinilreview.net read more . Paul GrintCMO, Regulus What is Alport syndrome and who does it affect? Alport Syndrome was initially described by your physician called Cecil Alport, back in the past due 1920s. It's a genetic disease that affects a certain type of collagen involved in the working of the kidney, the ear, and the eye. Primarily, when people discuss Alport Syndrome, they're considering kidney disease, but several these patients do also have impaired hearing and impaired vision. As a genetic disease, Alport syndrome can affect anybody in the genetic inheritance collection concerned. Probably about 75 percent of the transmitting is what we call X-linked, so inherited through the X chromosome. The condition therefore affects males. In the rest of cases, the problem isn’t X-linked and the inheritance rate is comparable between females and males. Depending on the nature of the genetic mutation, the age at which the syndrome starts to cause symptoms varies. Overall, you tend to see patients initially presenting with symptoms of renal disease at some true point within their teens. Quite often, they shall possess hematuria or blood in the urine, but are usually feeling well, which is usually the reason they visit the doctor. There's a cascade of investigations the doctor undertakes because then, as long as no urinary tract infection is present, healthy people should not have blood or proteins in their urine. How much happens to be known about the sources of Alport syndrome? Quite a lot is in fact known about the complexities with regards to the genetic defect impacting particular collagen molecules. Certain genes code for all those molecules, which have become important with regard to the anatomy of the kidney. The collagen molecules are assembled in an arrangement referred to as the basement membrane, which is critical in allowing the kidney to function as an effective filter of waste products. In Alport syndrome, because the basement membrane collagen isn’t constructed correctly, the kidneys basically fail to function properly and, over time, inflammation and therefore fibrosis develop. Why is the condition understood? We understand quite a complete lot about the disease procedure and about the genetics, but Alport syndrome isn’t an extremely common disease and there are no accepted therapeutic interventions for these individuals. Basically, patients are monitored and diagnosed, originally by a pediatric endocrinologist perhaps, and then referred to major centers. For example, in the UK, I believe you'll find the Great Ormond Street includes a large amount of experience because teens identified as having the condition are looked after there. The teens are monitored and finally their renal function declines to the stage where they want dialysis or a kidney transplant. However, a great way that people understand disease inside our industry is to study it in comprehensive controlled clinical studies. What are the main renal function markers and why is it vital that you study how they decline in Alport syndrome individuals over time? There are a number of different markers that people follow to assess kidney function generally. The kidney can be an important organ in your body for filtering waste material and you can actually just measure the levels of those, both in the bloodstream and the urine. One good examples is certainly creatinine, a by-product of muscle fat burning capacity. The degrees of creatinine are generally well established in a healthy body with normal kidney function. Creatinine is certainly excreted by the kidney in to the urine actively, but as the kidney function declines, the creatinine level in the blood rises. Creatinine is therefore an excellent marker of kidney function and needs just a simple blood check. Another waste product that is relatively simple to test for is bloodstream urea nitrogen . This is the level of nitrogen in the blood that originates from urea, the breakdown item of protein. Urea can be excreted through the kidney and as kidney function declines, the BUN level in the blood rises. We can also assess kidney function fairly accurately using something known as the glomerular filtration price , which assesses the function of the glomerulus, a framework which is primarily involved in handling the excretion of waste materials from the body. There are different ways of assessment the GFR. Then, you measure the known levels of that chemical in both the blood and the urine over time. In addition, there are additional biomarkers one can appearance at such as beta-2 microglobulin. As we're working in the microRNA space and know that we can detect microRNAs both in blood and in urine, all of us'll also be seeking at those microRNAs within our trials. Related StoriesGlan Clwyd Hospital N Wales spend money on Esaote's G-Scan MRI unit for weight-bearing scanningMedUni Vienna experts discover genetic cause of a rare diseaseUnderstanding how schizophrenia affects workings of the brainFinally, a renal biopsy can also be used to assess renal function. A needle can be used to take a small sample of tissue from the kidney, which is after that examined with special spots to measure the amount of inflammation histologically, fibrosis or whatever is in it. However, this is a distressing procedure for the individual and it is often only performed to confirm diagnosis in instances of chronic kidney disease. Most of the other markers I just described involve the blood or urine sample, so they are applied to a more schedule basis. What do you consider would be the main problems in increasing our knowledge of Alport syndrome? I think we have a good sense of the condition with regards to its inheritance pattern and exactly what happens to individuals who develop the disease. With regards to therapeutic intervention, we need to create the endpoints that could be found in a clinical research to assess the ramifications of the intervention on confirmed measure. Certainly, in this patient population the most desired outcome would be to arrest the disease and prevent its progression. If that is not possible, the aim is to significantly gradual disease progression in order that rather than patients developing end-stage renal disease by their late 20s, it could be delayed until the past due 30s, 40s, or actually later. We need to look at measures that we can reproducibly analyze as part of the clinical study, perhaps by examining the difference between an organization receiving treatment and an organization not receiving treatment. That's what we want to try and do basically, but the formal procedure for getting a drug approved and establishing those endpoints needs to be agreed both in america with the FDA and with the European Medications Agency in Europe, in order that regulators agree that the endpoints found in the clinical protocols are ideal for assessing the efficacy of the medication. What do you think the future keeps for Alport syndrome individuals? I believe the good news is that, as fresh therapeutic interventions are presented to these orphan disease populations, people shall start paying more focus on the patients also to the disease. There are several great patient support groups that are trying to educate people about how exactly Alport syndrome is a genetic disease which may be considered as a possible medical diagnosis whenever there are even the earliest indicators of kidney disease. The checks used to identify Alport syndrome are simple genetic tests relatively, yet a true quantity of healthcare systems in the US will not reimburse for those tests. I believe that as this patient group starts to create noise, it might push for earlier medical diagnosis. I believe the doctors who look after these patients really can start to think about working with the patients and with businesses like us, with regard to studying therapeutic interventions. I think overall, people can pay more attention to the disease, which at the end of the day is normally a great thing in terms of the patients' outcome. We've started our Athena study, a natural history study that is enrolling patients right into a formal clinical protocol currently. We are frequently testing these sufferers to monitor their renal function and a number of other things as time passes, so we are able to assess what the organic progression of the condition is in a potential manner. That research has were only available in the US now. We hope we are able to use the information out of this study to talk to both the FDA and EMA concerning endpoints and possible designs for a Phase 2 study, which we wish to start about a year from now. We're currently trying to gather all the right paperwork to put together an Investigational New Medication application. We will also be able to file all of that paperwork in Europe later on. The IND will allow us to accomplish some initial function in america using healthful volunteers to help us better understand the kinetics of this drug. You want to examine different subcutaneous dosages to observe how much enters the bloodstream and how much is certainly excreted through the kidney. We'll carry out some of that ongoing function over the first half of next year, and then continue steadily to focus on the Phase 2 design with a number of the essential opinion leaders and with regulatory organizations. That's our arrange for the near future. Where can readers find more info? Users can find more information at the Regulus internet site, regulusrx.com. At the bottom right hands corner of the homepage, there is information regarding the Athena scientific trial where people may also connect to the alportstudy.com site. That site is because really beneficial to look at, as we discussed, this is a patient population that hasn't been involved in clinical research before really. The web site provides background information about being a individual in a clinical trial. We need the patients' dedication and support to come quickly to their clinic visits, agree to the blood tests, and other activities. We need the clinical research to be a partnership between us, the individuals and the doctors looking after these sufferers, if we're going to achieve success in moving the scientific program forwards. About Dr Paul Grint Dr. Grint joined Regulus in June 2014 with over 2 decades of experience in biologics and little molecule development, like the successful commercialization of several commercial items in oncology, anti-infectives and immunology in both domestic and international markets. To joining Regulus Prior, Dr. Grint was President of Cerexa, Inc., a wholly-possessed subsidiary of Forest Laboratories, Inc., where he was in charge of the oversight of anti-infective product development. Prior to that, Dr. Grint served as Senior Vice President of Analysis at Forest Analysis Institute, Inc., Chief Medical Officer at Kalypsys, Inc., and Senior Vice Chief and President Medical Officer at Zephyr Sciences, Inc., and he served in similar executive level positions at Pfizer Inc also., IDEC Pharmaceuticals Corporation, and Schering-Plough Corporation. Dr. Dr. Grint is definitely a Fellow of the Royal College of Pathologists, a member of numerous professional and medical societies, and the writer or co-writer of over fifty scientific publications. Continue reading Alport syndrome: an interview with Dr Paul Grint http://modafinilreview.net.